Combined Use of Warfarin and Aspirin Decreases Mortality in Patients with Peripheral Arterial Disease.

Anti-platelet therapy with aspirin (ASA) is standard therapy for patients with peripheral arterial disease (PAD). While ASA is not felt to impact the natural history of PAD, it decreases mortality from stroke, myocardial infarction, and other co-morbidities in the patients with PAD. Anticoagulation with warfarin (WAR) is indicated in arterial and venous thrombo-embolic conditions such as deep vein thrombosis and atrial fibrillation, but is generally considered not beneficial in patients with PAD. We retrospectively identified patients via ICD9 code who were diagnosed with PAD between January and December 2000, and assessed their course through July 2005. Of 530 individuals, 45 had a history of taking ASA and WAR concomitantly, 116 of taking WAR alone, 219 of taking ASA alone, and 150 received neither drug. Age, mortality, prevalence of hemorrhage and of co-morbid conditions (smoking, diabetes mellitus, atrial fibrillation, stroke, myocardial infarction, hypertension, coronary artery disease, hyperlipidemia, congestive heart failure, renal failure, and chronic obstructive pulmonary disease) that could affect mortality or hemorrhage were determined. Results are illustrated in the table.

The higher number (not statistically significant) of co-morbid conditions in patients receiving WAR was because most of these individuals had atrial fibrillation. We observed a significant decrease in mortality in patients receiving WAR+ASA compared to patients on WAR alone (Chi-square, p=0.044) and neither drugs (p=0.014), and a trend for decreased mortality compared with patients on ASA alone (p=0.062). However, we observed an increased prevalence of hemorrhage in patients receiving WAR with or without ASA compared with individuals receiving ASA alone (WAR vs ASA p=0.016; WAR+ASA vs ASA p=0.002). We suspect that the frequent hemorrhagic events observed in individuals on neither drug may in part explain why these individuals were not on ASA and/or WAR. This retrospective data suggests combination therapy with WAR+ASA may be better than either agent alone or no therapy for reducing mortality in patients with PAD. Further, this data suggests that the pathogenesis of PAD may involve both platelet and non-platelet mediated hypercoagulable states.